Impact of sex hormones dysregulation and adiposity on the outcome of postmenopausal breast cancer patients.

Epidemiological studies demonstrated that, in postmenopausal women, high circulating levels of testosterone, especially when associated with weight gain, positively correlated with an increased risk of breast cancer because of the augmented production of oestrogen via testosterone aromatization in the adipose tissue. Besides, growing evidence suggests that sulfatase can increase the tissue concentration of bioactive estradiol through the reconversion of estrone sulfate, thus providing a favourable milieu for epithelial cells expressing the oestrogen receptor. In this review, we will discuss how the "obesity-insulin-testosterone" connection and the abnormal production of bioactive oestrogen - as a result of the conversion of the androgens by aromatase and the estrone reconversion by sulfatase-, may affect the response to hormone therapy and the outcome of postmenopausal breast cancer patients, and how a combined therapy including metformin, anti-inflammatory drugs, and aromatase/sulfatase inhibitors could successfully improve patient's outcome.